Samarium enolates synthesis

Benzenetricarbonyl trichloride and l,2,4,5-tetrakis(bromomethyl) benzene were employed as multifunctional initiators for the synthesis of 3-and 4-arm PTHF stars, respectively [147]. The living ends were reacted with sodium 2-bromoisobutyrate followed by reduction with Sml2. The samarium enolates, thus formed were efficient initiators for the polymerization of MMA to give the (PTHF-fo-PMMA) , n = 3 or 4 star-block copolymers, according to Scheme 71. 

Samarium enolates 60 can be easily prepared by reduction of ct-bromocarboxylic acid esters with SmT. These enolates mediated well-defined synthesis of star-shaped block co-polymers 61 (Scheme 21 ).32 32l Sml3 also mediated the formation of samarium enolates. Phenacyl thiocyanate 6233 and cr-haloketone 6434 are converted to samarium(lll) enolate intermediates 63 and 65, respectively, which undergo addition to benzaldehyde derivatives affording the corresponding oy i-unsaturatcd ketones as shown in Schemes 22 and 23. 

Condensation reactions with donor species generated by reductive cleavage of a-sub-stituted carbonyl compounds are regioselective. Thus, the synthesis of a-(l-hydrox-yalkyl)-P-ketols is quite straightforward from a, 5-epoxy ketones. Samarium enolates derived from a-(pyridylthio)glycyl peptides are also applicable to the synthesis of unnatural peptides by reaction with various carbonyl compounds. ... 

The group of Boger described the total synthesis of kopsinine, a member of the Aspidosperma alkaloids, using their landmark [4 + 2]/[3 + 2] cycloaddition cascade for the conversion of 44 to 45 (Scheme 16). An unusual Sml2-promoted transannular cyclisation of xanthate 46, formed the bicyclo[2,2,2]octane moiety and provided the highly compact core of the natural product 48 as a single diastereoisomer. Although 48 is the least stable diastereoisomer, its formation is consistent with a radical cyclisation mechanism followed by kinetic protonation of the samarium enolate 47 formed after a second electron transfer. 

The samarium-catalyzed reduction was utilized in the asymmetric synthesis of the marine macrolide bryostatin 2 (42) to furnish an intermediate (46)12 (Scheme 4.21). The ketone 43 underwent an aldol reaction with the ketoaldehyde 44 via the isopinylboryl enolate to give the aldol adduct 45 in good yield and 93 7 diastereoselectivity. Subsequent samarium-catalyzed Evans-Tishchenko reduction of the (3-hydroxy ketone 45 provided the p-nilrobenzoale 46 with excellent stereoselectivity. Silylation and saponification readily converted compound 46 into the alcohol 47 in 88% yield over two steps. 

In the synthesis of the marine macrolide leucascandrolide A (54), Kozmin used the samarium-catalyzed diastereoselective ketone reduction method in a highly stereocontrolled synthesis of the C1-C15 fragment 5814 (Scheme 4.2n). Generation of the dicyclohexylboron enolate of the ketone 55 followed by addition... 

An early intermediate (203) in the synthesis of paeoniflorigenin (204) by Corey was prepared from the silyl enol ether 202 and cyanoacetic acid under the Mn(III)-mediated radical addition conditions [133] (Scheme 69). Highly enantioselective synthesis of y-lactones was reported by Fukuzawa [134] (Scheme 70). The crotonate 205 derived from A-methylephedrine reacted with pentanal in the presence of Sml2 to yield the lactone 206 suggesting chelation control by samarium in the ketyl addition step. 

Synthesis of Alkenes by Reductive Elimination. The treatment of 2-halo-3-hydroxy esters and amides with samarium iodide leads to the corresponding di- or trisubstituted E)-a,p-unsaturated derivatives in high yields and diastereoselectivities (eqs 39 and 40). The precursors are readily accessible by condensation of the lithium enolate of a-haloesters or amides. If the substrate contains y,i5-unsaturation, the /3,y-unsaturated ester is generated in the process (eq 41). 

Synthesis of Homoenolate Equivalent. The samarium iodide-induced coupling of carbonyl derivatives with methoxyal-lene provides 4-hydroxy 1-enol ethers in high yields (eq 58). An almost equimolar mixture of the two enol ethers are usually observed but acid hydrolysis leads to the aldehyde. 

The synthesis began with Prins qrchzation of the symmetric vinylo-gous ester 273, prepared from heptadienol 272, followed by hydrolysis of the resulting trifluoroacetate and benzylation, to afford the desired 2,6-cis-tetrahydropyran 274 with 92 8 diastereoselection at C5 [113], By this novel desymmetrization, 2,4,6-all-ci5 trisubstituted pyran was efficiently provided. Boron-enolate aldol reaction, as Carreira did, of the methyl ketone 274 with aldehyde 275 gave hydroxy ketone 271 as a single isomer. In contrast to Car-reira s result, samarium-catalyzed intramolecular Tishchenko reduction [114]... 

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